The objective of this work is to advance CNS drug development by the transfer of novel metabolic imaging technology for application during Phase I and Phase II clinical trials. In this application the plasma dose curve and associated metabolic tissue changes will be measured as acute and long-term effects for the SSRI, fluoxetine at two different administered doses. Normal subjects will be studied in a double-blind, crossover study comparison to placebo. The method includes novel adaptations of established methods for measuring rCMRglu with PET. It measures the downstream changes in regional glucose metabolism that are the net end-effect of the drug-receptor interaction and sequentially induced postsynaptic responses. Offering a new basis for strategic planning, the approach provides quantitative measurements of dose response and drug effect that will accelerate the early development phases, enhance cost effectiveness of the process, and help bring more new drugs to market at lower unit cost. PROPOSED COMMERCIAL APPLICATION: Commercialization of this method will entail the development of a unique imaging service, which will be marketed to the pharmaceutical industry for the evaluation of CNS compounds prior to Phase II trials. This will aid in strategic planning and significantly shorten CNS drug development time by providing previously unavailable information in human subjects during the earliest stages of clinical development.